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Galectin 4 bridging the gap in cardiometabolic disease predicting diabetes, coronary events and mortality in a Swedish population cohort

Session The basic science of diabetes and the metabolic syndrome

Speaker John Molvin

Event : ESC Congress 2018

  • Topic : basic science
  • Sub-topic : Basic Science - Cardiac Diseases: Biomarkers
  • Session type : Rapid Fire Abstracts

Authors : J Molvin (Lund,SE), M Pareek (Holbaek,DK), O Melander (Lund,SE), L Rastam (Lund,SE), U Lindblad (Gothenburg,SE), B Daka (Gothenburg,SE), M Leosdottir (Lund,SE), P Nilsson (Lund,SE), MH Olsen (Holbaek,DK), M Magnusson (Lund,SE)

Authors:
J. Molvin1 , M. Pareek2 , O. Melander3 , L. Rastam3 , U. Lindblad4 , B. Daka4 , M. Leosdottir1 , P. Nilsson3 , M.H. Olsen2 , M. Magnusson1 , 1Lund University, Department of Heart Failure and Valvular Disease, Skåne University Hospital Malmö, Sweden - Lund - Sweden , 2Holbaek Hospital - Holbaek - Denmark , 3Lund University - Lund - Sweden , 4Sahlgrenska Academy - Gothenburg - Sweden ,

Citation:
European Heart Journal ( 2018 ) 39 ( Supplement ), 1077

Background: We recently conducted a proteomic exploration of 92 potential biomarkers for incident diabetes and found a novel association for the lectin, galectin-4, with incident diabetes, independently of fasting glucose and traditional risk factors for diabetes. Galectin-4 is expressed almost exclusively in the intestinal tract and has mostly been associated with malignancies, but may also play a role in the incretin system. In light of our novel finding, our aim was to investigate whether galectin-4 is associated with incident major adverse coronary events (MACE), incident heart failure (HF), cardiovascular mortality (CVM), and all-cause mortality (ACM).

Methods: 92 proteins from the Proseek Multiplex CVD III (Olink Bioscience, Sweden) were analyzed in 1737 participants from a subsample of the population-based Malmö Preventive Project (mean age 67 years, 29% women). For the analysis of incident MACE, subjects with prevalent coronary disease (n=191) and missing covariate data (n=2) were excluded. 1544 subjects (166 incident cases vs. 1378 controls; median follow up time 8.8 years) remained. For HF, subjects with prevalent HF (n=32) and missing covariate data (n=6) were excluded. 1699 subjects (91 cases vs. 1608 controls) remained. For CVM, 1713 subjects (109 cases vs. 1604 controls, 8.8 years) and ACM 1644 subjects (315 cases vs. 1329 controls, 9.0 years) were analyzed. Multivariable Cox regression models adjusted for age, sex, systolic blood pressure, diastolic blood pressure, antihypertensive therapy, total cholesterol, high-density lipoprotein cholesterol, regular cigarette smoking, body mass index, and presence of diabetes mellitus were used to calculate hazard ratios.

Results: After adjustment for cardiovascular risk factors, each 1 standard deviation (SD) of increase in galectin-4 was associated with incident MACE (hazard ratio (HR) 1.24 (95% confidence interval (CI) (1.05–1.46)), p=0.013). For the analysis of risk of incident HF, prevalent atrial fibrillation and prevalent coronary disease were added as covariates on top of the abovementioned cardiovascular risk factors and resulted in a HR (per SD) 1.34 (1.05–1.70; p=0.019). For the analysis of the risk of ACM, echocardiographic left ventricular hypertrophy was included as well as prevalent atrial fibrillation, heart failure and coronary disease on top of traditional risk factors resulting in a HR (per SD) 1.46 (1.29–1.66), p=5.62x10–9. Finally, for the analysis of CVM, prevalent coronary disease and heart failure were included on top of the traditional risk factors, resulting in a HR (per SD) 1.46 (1.15–1.85), p=0.002.

Conclusion: A tandem-repeat lectin, galectin-4, recently associated with incident diabetes is also associated with cardiovascular disease as defined by incident MACE, incident heart failure, cardiovascular mortality, and all-cause mortality.

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